Human stem cell models of Alzheimer’s disease
Award Number
101052/Z/13/ZAward Type
Investigator Awards in ScienceStatus / Stage
CompletedDates
1 August 2013 -31 July 2019
Duration (calculated)
05 years 11 monthsFunder(s)
Wellcome TrustFunding Amount
£2,063,349.00Funder/Grant study page
Wellcome TrustContracted Centre
University of CambridgePrincipal Investigator
Prof Frederick LiveseyPI Contact
r.livesey@ucl.ac.ukPI ORCID
0000-0001-6128-3372WHO Catergories
Models of DiseaseUnderstanding Underlying Disease
Disease Type
Alzheimer's Disease (AD)CPEC Review Info
| Reference ID | 328 |
|---|---|
| Researcher | Reside Team |
| Published | 12/06/2023 |
Data
| Award Number | 101052/Z/13/Z |
|---|---|
| Status / Stage | Completed |
| Start Date | 20130801 |
| End Date | 20190731 |
| Duration (calculated) | 05 years 11 months |
| Funder/Grant study page | Wellcome Trust |
| Contracted Centre | University of Cambridge |
| Funding Amount | £2,063,349.00 |
Abstract
We propose to use stem cell models of Alzheimer’s disease to ask and answer biological questions about the disease that have not been previously approachable: the study of AD initiation and pathogenesis in human forebrain neuronal networks, in real time. This programme depends on our fundamental research in developmental and stem cell biology and neuroscience, and associated technologies, such as genome engineering and imaging. That research underpins our ability to generate in vitro, glutamater gic cortical neural networks, which are the basis for functional studies of AD biology. We have used that system to study the development of Alzheimer’s disease pathologies in Down syndrome, including greatly increased Abeta peptide production, the formation of extracellular Abeta aggregates, changes in Tau phosphorylation and cellular localisation, release of extracellular Tau and cell death. Based on that work, we now propose to generate models of familial and sporadic Alzheimer’s disease, and use these models for functional experiments that address specific questions in AD: – How does AD progress and spread through the human nervous system? – How does AD affect neuronal function at the synapse and network level? – Can those changes be reversed? – How do AD-associated genetic variants contribute to disease initiation and progression in sporadic, late onset AD?
Aims
Dr Livesey plans to build on his previous work, which led to the development of stem cell models of AD, to generate insights into AD initiation, progression and therapeutic intervention. Specifically, he will investigate how AD progresses and spreads through the human nervous system, and how AD affects neuronal function at the synapse and network level. He will also study AD-associated genetic variants and how these contribute to disease initiation and progression in sporadic, late-onset AD. By examining the causes and mechanisms of AD initiation and progression, it is hoped that these can be reversed and that new therapeutic interventions can be developed.